CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, Anhui 230027, China.
State Key Laboratory of Nonlinear Mechanics, Institute of Mechanics, Chinese Academy of Sciences, 15 Beisihuan West Road, Beijing 100190, China.
ACS Nano. 2024 Aug 13;18(32):21144-21155. doi: 10.1021/acsnano.4c03667. Epub 2024 Aug 1.
Cells can sense the physical properties of the extracellular matrices (ECMs), such as stiffness and ligand density, through cell adhesions to actively regulate their behaviors. Recent studies have shown that varying ligand spacing of ECMs can influence adhesion size, cell spreading, and even stem cell differentiation, indicating that cells have the spatial sensing ability of ECM ligands. However, the mechanism of the cells' spatial sensing remains unclear. In this study, we have developed a lattice-spring motor-clutch model by integrating cell membrane deformation, the talin unfolding mechanism, and the lattice spring for substrate ligand distribution to explore how the spatial distribution of integrin ligands and substrate stiffness influence cell spreading and adhesion dynamics. By applying the Gillespie algorithm, we found that large ligand spacing reduces the superposition effect of the substrate's displacement fields generated by pulling force from motor-clutch units, increasing the effective stiffness probed by the force-sensitive receptors; this finding explains a series of previous experiments. Furthermore, using the mean-field theory, we obtain the effective stiffness sensed by bound clutches analytically; our analysis shows that the bound clutch number and ligand spacing are the two key factors that affect the superposition effects of deformation fields and, hence, the effective stiffness. Overall, our study reveals the mechanism of cells' spatial sensing, i.e., ligand spacing changes the effective stiffness sensed by cells due to the superposition effect of deformation fields, which provides a physical clue for designing and developing biological materials that effectively control cell behavior and function.
细胞可以通过细胞黏附来感知细胞外基质（ECM）的物理性质，如硬度和配体密度，从而主动调节细胞行为。最近的研究表明，改变 ECM 中的配体间距可以影响黏附大小、细胞铺展，甚至干细胞分化，这表明细胞具有 ECM 配体的空间感知能力。然而，细胞的空间感知机制尚不清楚。在本研究中，我们通过整合细胞膜变形、talin 展开机制和基质配体分布的晶格弹簧，开发了一种晶格弹簧马达离合器模型，以探索整合素配体的空间分布和基质硬度如何影响细胞铺展和黏附动力学。通过应用 Gillespie 算法，我们发现较大的配体间距会降低由马达离合器单元产生的拉力引起的基质位移场的叠加效应，从而增加力敏感受体探测到的有效刚度；这一发现解释了一系列先前的实验。此外，我们使用平均场理论，从理论上分析了被束缚的离合器所感知的有效刚度；我们的分析表明，束缚的离合器数量和配体间距是影响变形场叠加效应进而影响有效刚度的两个关键因素。总的来说，我们的研究揭示了细胞空间感知的机制，即配体间距通过变形场的叠加效应改变细胞所感知的有效刚度，这为设计和开发能够有效控制细胞行为和功能的生物材料提供了物理线索。
